Rheumatic diseases are a group of diseases that effect the musculo-skeletal and connective tissues of the body. Such diseases are characterized by chronic inflammation which often leads to permanent tissue damage, deformity, atrophy and disability. Rheumatoid arthritis, a progressive rheumatic disease, affects as many as 1-2% of all adults [P. D. Utsinger et al., Rheumatoid Arthritis, p. 140 (1985)].
Although their etiology is unknown, most rheumatic diseases are thought to be autoimmune diseases caused by a patient's altered immune response to as yet unidentified antigen or antigens [H.O. McDevitt and B. Benacerraf, "Genetic Control Of Specific Immune Responses", Adv. Immunol., 11, p. 31 (1969)].
Rheumatic diseases may affect the joints, spinal cord, soft tissue or bone [H. Mathies, Rheuma ("Rheumatism") (1983)]and are classified as inflammatory rheumatism, degenerative rheumatism, extraarticular rheumatism or collagen diseases. Systemic lupus erythematosus, progressive systemic scleroderma, dermatomyositis, chronic polyarthritis, psoriasis arthropathica, muscular rheumatism, periarthritis humeroscapularis, panarteriitis nodosa, myositis, myogelosis, arthritis uratica and chondrocalcinosis are also rheumatic diseases [W. Pschyrembel, Klinisches Worterbuch ("Medical Dictionary") (1982)]. Juvenile chronic arthritis, which occurs in children and adolescents, differs from rheumatoid arthritis as seen in adults and can lead to impaired development and growth [B. Z. P. Anzell, "Juvenile Chronic Polyarthritis", Arthr. Rheum. Supp., 20, pp. 176-80 (1977); H. Truckenbrodt, "Die Juvenile Chronische Arthritis Und Ihre Subgruppen" ("Juvenile Chronic Arthritis And Its Subgroups"), Munch. Med. Wschr., 126, pp. 1076-78 (1984). Upon serological examination, the majority of patients diagnosed with clinical rheumatic disease test seropositive for rheumatoid factor, an abnormal gamma-globulin [R. B. Berkow et al. (Eds.), The Merck Manual (1982)].
Because the etiology of the majority of rheumatic diseases remains unknown, no cure for these diseases exists and effective agents are not conventionally available for treatment of a specific disease [K. Kruger, "Neue Therapieprinzipien In Der Rheumatologie" ("New Therapeutic Principles In Rheumatology"), Munch. Med. Wschr., 126, pp. 1084-86 (1984)]. Moreover, these agents typically must be administered over long periods of time and any therapeutic value is often diminished by adverse side effects.
Therapeutics used in the treatment of rheumatic diseases fall into two classes. The first class of therapeutics, symptomatic anti-rheumatics, act on the symptoms of the disease, exerting effects both upon and throughout the total course of administration. Such symptomatic anti-rheumatics include salicylic acid, glucocorticoids and non-steroidal anti-inflammatory agents, such as inodomethacin. The second class of therapeutics, base anti-rheumatics, act on the pathogenesis of the disease, exerting their effects only after the initial weeks of administration yet having effects lasting beyond the cessation of treatment. Such base anti-rheumatics include gold compounds, D-penicillamine, chloroquine, cortisones and immunosuppressants [H. Mathies, Rheuma, infra, p. 1; R. C. Butler and D. H. Goddard, "Controversy In The Treatment Of Rheumatoid Arthritis", Lancet, ii, pp. 278-79 (1984)].
These prior therapeutic agents are often characterized by adverse side effects. For example, those that are immunosuppressants may increase the patient's susceptibility to infection. And, therapies based on gold compounds, penicillamine or chloroquine may exert toxic effects on the patient's system.
Alpha interferon has been reported to be ineffective in the treatment of rheumatoid arthritis [A. Kajender et al., "Interferon Treatment Of Rheumatoid Arthritis", Lancet, i, pp. 984-85 (1979)]. This lack of efficacy may not be surprising because certain rheumatic diseases, such as rheumatoid arthritis, are characterized by an endogenous formation of interferons to which no therapeutic activity has been ascribed. Furthermore, in some cases, high circulating levels of interferons have been suggested without real clinical data as a factor contributing to the pathogenesis of rheumatic diseases [J. J. Hooks et al., "Immune Interferon In The Circulation Of Patients With Autoimmune Disease", N. Engl. J. Med., 301, pp. 5-8 (1979); O. T. Preble et al., "Systemic Lupus Erythematosus: Presence In Human Serum Of An Unusual Acid-Labile Leukocyte Interferon", Science, 126, pp. 329-31 (1982); M. Degre et al., "Immune Interferon In Serum And Synovial Fluid In Rheumatoid Arthritis And Related Disorders", Ann. Rheumatic. Dis., 42, pp. 672-76 (1973); A. M. Arvin and J. J. Miller, "Acid Labile .alpha.-Interferon In Sera And Synovial Fluids From Patients With Juvenile Arthritis", Arthritis and Rheumatism, 27, pp. 582-85 (1984); T. 0. Rosenbach et al., "Interferon Triggers Experimental Synovitis And May Potentiate Auto-Immune Disease In Humans", Clin. Rheumatol., 3, pp. 361-64 (1984)].
To date therefore, conventional methods and therapeutic agents have not proved to be effective in the treatment of rheumatic diseases. Accordingly, the need exists for a process which avoids the disadvantages of these conventional methods and agents while providing effective treatment for rheumatic diseases.